Fig. 6: IFT-A disease mutations.
From: Human IFT-A complex structures provide molecular insights into ciliary transport
a IFT-A disease mutations are mapped based on disease types. SRTD short-rib thoracic dysplasia, CED cranioectodermal dysplasia, SLSN Senior-Loken syndrome, RP retinitis pigmentosa, JBTS Joubert syndrome, NPHP nephronophthisis, ATD asphyxiating thoracic dystrophy. Note: for a complete mapping of the disease mutations, we modeled the WD40-A of IFT140 with the following approach: we took the AF2 model of IFT140 WD40 domains and then aligned with our resolved WD40-B to get the position of WD40-A. b Left: Role of IFT140 in TULP3 binding. Right: FSEC traces of IFT-A complex formation with or without IFT-140 by monitoring the GFP fluorescence of GFP-IFT43. c Impact of Ift140 KO on ciliary transport. WT and Ift140 KO MEFs were serum starved upon confluency for 48 h before fixation. Fixed cells were immunostained for ARL13B or GPR161, acetylated tubulin, γ-tubulin, and counterstained for DNA (shown in Supplementary information, Fig. S9a, b). Cilia were counted from 2 coverslips each from 2 experiments, n > 300/condition. Data represent mean ± SD. ****P < 0.0001 with respect to WT. d Interaction details surrounding Trp174 at the interface between the HC–HD region of IFT43 and the ZBS of IFT121. e IFT-A complex formation in the presence of GFP-tagged IFT43W174 mutants with or without adding detergents. IFT-A complex amount (y-axis) is calculated by integrating the chromatography peak and normalized to WT (n = 3). f The IFT-A complex formation in the presence (gray) and absence (magenta) of GFP-IFT43 by FSEC.
